1. Volume 25, Issue 3, Pages 506-513 (March 2017)
Allosteric Mutant IDH1 Inhibitors Reveal Mechanisms for IDH1 Mutant and Isoform Selectivity 
Xiaoling Xie, Daniel Baird, Kimberly Bowen, Vladimir Capka, Jinyun Chen, Gregg Chenail, YoungShin Cho, Julia Dooley, Ali Farsidjani, Pascal Fortin, Darcy Kohls, Raviraj Kulathila, Fallon Lin, Daniel McKay, Lindsey Rodrigues, David Sage, B. Barry Touré, Simon van der Plas, Kirk Wright, Ming Xu, Hong Yin, Julian Levell, Raymond A. Pagliarini 
Structure 
Volume 25, Issue 3, Pages (March 2017)
DOI: /j.str
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2. Structure 2017 25, 506-513DOI: (10.1016/j.str.2016.12.017)
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3. Figure 1
Structures of Two Mutant- and Isoform-Selective IDH1 Inhibitors Bound to IDH1R132H
(A) Small-molecule structure and activity profile of IDH125.
(B) Small-molecule structure and activity profile of IDH146.
(C) Structure of dimeric IDH1R132H with IDH125 bound (PDB: 5SVF). Individual monomers are shown in yellow and light blue. The partially ordered α10 regulatory segment for each monomer is shown in dark blue. NADPH is shown in gray, and IDH125 is shown in magenta.
(D) Structure of IDH1R132H with IDH146 bound (PDB: 5SUN), as in (C). Note that the α10 regulatory segment is not resolved in this structure.
(E) Close up of the IDH125 binding site, with secondary structures labeled as in Xu et al. (2004). Dotted lines denote hydrogen bond interactions.
(F) Close up of the IDH146 binding site, as in (E).
Structure  , DOI: ( /j.str )
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4. Figure 2
Regulatory Helix Instability Regulates Inhibitor Binding to IDH1
(A) Steady-state SPR sensogram for IDH125 binding to IDH1R132H (top graph) and IDH1WT (bottom graph) in the presence Mg2+.
(B) SPR sensogram as in (A), but in the absence of Mg2+.
(C) Activity of 583 compounds of the same structural class as IDH125 in biochemical assays measuring NADPH production in IDH1WT (y axis) versus NADPH consumption in IDH1R132H (x axis). IDH662 is shown in red.
(D) Small-molecule structure of IDH662 and associated activity profile.
Structure  , DOI: ( /j.str )
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5. Figure 3 Intrinsic Stability of the IDH2 α10 Helix
(A) Structure of IDH2R172K (PDB: 5SVN), colored as in Figure 1A.
(B) Structure of IDH2R140Q (PDB: 5SVO), colored as in Figure 1A.
(C) Close up of the IDH2R172K active site, highlighting the positions of K172 and N310.
(D) Top-down view through the IDH2R172K dimer interface, with I319 of the α10 helix from each monomer (dark blue) shown as sticks.
(E) Top-down view through the IDH1R132H dimer interface, as in (D). S280 from each α10 regulatory segment is shown as sticks, and waters are shown as red dots.
(F) Close up of the IDH1R132H allosteric pocket (blue) bound to IDH125 (magenta), with the IDH2R140Q structure overlaid (gray).
Structure  , DOI: ( /j.str )
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6. Figure 4
Mutation of A111 in IDH1 to Its Analogous IDH2 Residue Reduces IDH1 Inhibitor Potency
(A) Left: surface representation of the IDH1R132H allosteric pocket, with alanine 111 highlighted. IDH125 is represented in magenta. Right: model (see Supplemental Experimental Procedures) of proline (the analogous residue in IDH2) in the IDH1 pocket, colored as in the left panel.
(B) 2-HG production in MCF10A cells expressing exogenous IDH1R132H (black circles) or IDH1R132H, A111P (red squares), with increasing concentrations of IDH125 (top panel) or IDH662 (bottom panel). Error bars indicate SD of three replicates.
(C) Proliferation of MCF10A cells expressing exogenous IDH1R132H (black circles) or IDH1R132H, A111P (red squares), with increasing concentrations of IDH125 (top panel) or IDH662 (bottom panel). Error bars indicate SD of three replicates.
Structure  , DOI: ( /j.str )
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